Faculty Bibliography

The LMO2/LDB1 macromolecular complex is critical in hematopoietic stem and progenitor cell specification and in the development of acute leukemia. This complex is comprised of core subunits of LMO2 and LDB1 as well as SSBP cofactors and DNA binding bHLH and GATA transcription factors. We analyzed the steady state abundance and kinetic stability of LMO2 and its partners via Halo protein tagging in conjunction with variant proteins deficient in binding their respective direct protein partners. We discovered a hierarchy of protein stability, with half lives in descending order: LDB1>SSBP>LMO2>TAL1. Importantly, LDB1 is a remarkably stable protein that confers enhanced stability upon direct and indirect partners, thereby nucleating the formation of the multisubunit protein complex. The data imply that free subunits are more rapidly degraded than those incorporated within the LMO2/LDB1 complex. Our studies provide significant insights into LMO2/LDB1 macromolecular protein complex assembly and stability, which has implications for understanding its role in blood cell formation and for therapeutically targeting this complex in human leukemias.

PURPOSE/OBJECTIVE:The paranasal sinuses are complex anatomical structures of unknown significance. One hypothesis theorizes that the sinuses, in the event of a traumatic injury, function as a crumple zone to distribute and absorb energy to protect the brain and other critical structures. The current study investigates the association between frontal sinus (FS) volume and the severity of cerebral insults following craniofacial trauma. METHODS:All patients with FS fracture admitted to a level 1 trauma center from 2011 to 2014 were retrospectively reviewed. FS volumes were measured from computed tomography (CT) on admission using a proprietary region growing segmentation tool. Head injuries were classified based on the presence of specific types of intracranial pathology and their corresponding Marshall Score. RESULTS:, p < 0.001). Smaller FS volume was significantly associated with a worse Marshall Score (p = 0.041) and a higher incidence of cerebral contusion (p = 0.016) independent of age, gender, mechanism, ISS, and admission GCS. The inverse correlation between FS volume and the Marshall Score was also statistically significant (Spearman correlation coefficient r = -0.19, p = 0.015). Smaller FS volume was observed in patients who suffered intracranial insults, underwent neurosurgical interventions, and had worse clinical outcomes and trended towards significance with respect to an association with subarachnoid hemorrhage (p = 0.074) and subdural hematoma (p = 0.080), and had a statistically significant association with longer length of stay (p < 0.001). CONCLUSION/CONCLUSIONS:FS volume is inversely correlated with the severity of intracranial pathology following craniofacial trauma. Our findings are consistent with the "crumple zone" hypothesis and suggest that the FS likely plays a role in mitigating intracranial injury. Furthermore, FS volume is significantly different between male and female patients. This is a novel finding that warrants further validation.

Complex periorbital subunit reconstruction is challenging because the goals of effective reconstruction vary from one individual to another. The purpose of this article is to explore the indications and anatomic feasibility of periorbital transplantation by reviewing our institutional repository of facial injury. METHODS: Institutional review board approval was obtained at the R Adams Cowley Shock Trauma Center for a retrospective chart review conducted on patients with periorbital defects. Patient history, facial defects, visual acuity, and periorbital function were critically reviewed to identify indications for periorbital or total face (incorporating the periorbital subunit) vascularized composite allotransplantation. Cadaveric allograft harvest was then designed and performed for specific patient defects to determine anatomic feasibility. Disease conditions not captured by our patient population warranting consideration were reviewed. RESULTS: A total of 7 facial or periorbital transplant candidates representing 6 different etiologies were selected as suitable indications for periorbital transplantation. Etiologies included trauma, burn, animal attack, and tumor, whereas proposed transplants included isolated periorbital and total face transplants. Allograft recovery was successfully completed in 4 periorbital subunits and 1 full face. Dual vascular supply was achieved in 5 of 6 periorbital subunits (superficial temporal and facial vessels). CONCLUSIONS: Transplantation of isolated periorbital structures or full face transplantation including periorbital structures is technically feasible. The goal of periorbital transplantation is to re-establish protective mechanisms of the eye, to prevent deterioration of visual acuity, and to optimize aesthetic outcomes. Criteria necessary for candidate selection and allograft design are identified by periorbital defect, periorbital function, ophthalmologic evaluation, and defect etiology.

BACKGROUND:This study investigates the hypothesis that mechanisms of injury, fracture patterns, and burden to the health care system differ between geriatric and nongeriatric populations sustaining blunt-force craniofacial trauma. METHODS:A 5-year retrospective chart review of patient records and computed tomographic imaging was performed. Demographic and outcome data were extracted for equally numbered samples of blunt-mechanism facial fracture patients aged 60 years or older (geriatric), and adult patients aged 18 to 59 years (adult nongeriatric). Comparisons were made between these two populations using t tests and multivariable logistic regression. RESULTS:One thousand eighty-seven geriatric and 1087 nongeriatric patients were included. Geriatric patients were significantly more likely to be Caucasian, female, and have sustained fractures as the result of falling. They also had significantly longer hospital stays, were more likely to die, and were more likely to be discharged to home with services. Mandible fractures and panfacial fractures were significantly more common in the nongeriatric population. Geriatric age was associated with doubled length of hospitalization for patients with midface fractures. Logistic regression revealed that significantly higher incidences of orbital floor, maxillary, and condylar fractures in geriatric patients were dependent on geriatric age status, rather than mechanism of injury alone. CONCLUSIONS:Resource allocation for geriatric patients with craniofacial trauma should differ from that of their nongeriatric adult counterparts, with more resources allocated to supportive care during hospitalization and assistive care after discharge. The authors' data indicate that structural and biological changes in the craniofacial skeleton contribute to differences in fracture location independent of mechanism of injury. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Risk, II.

Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression must be pursued. Employing vascularized bone marrow transplantation and co-transplantation of the thymus have shown promise in this regard in various animal models. Vascularized bone marrow transplantation allows for the uninterrupted transfer of donor bone marrow cells within the preserved donor microenvironment, and the incorporation of thymus tissue with vascularized bone marrow transplantation has shown to increase T-cell chimerism ultimately playing a supportive role in the induction of immune regulation. The combination of solid organ and vascularized composite allotransplantation can uniquely combine these strategies in the form of a novel transplant model. Murine models serve as an excellent paradigm to explore the mechanisms of acute and chronic rejection, chimerism, and tolerance induction, thus providing the foundation to propagate superior allograft survival strategies for larger animal models and future clinical application. Herein, we developed a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique. The experience in syngeneic and allogeneic transplant settings is described for future broader immunological investigations via an instructional manuscript and video supplement.

BACKGROUND: Traumatic optic neuropathy is characterized by sudden loss of vision following facial trauma leading to variable visual deficits. The purpose of this study was to evaluate recent institutional trends in the treatment of traumatic optic neuropathy, evaluate the outcomes of different treatment strategies, and identify factors associated with improved vision. METHODS: Institutional review board approval was obtained to retrospectively review patients diagnosed with traumatic optic neuropathy at a high-volume trauma center from 2004 to 2012. Pretreatment and posttreatment visual acuity was compared using quantitative analysis of standard ophthalmologic conversion. RESULTS: A total of 109 patients met inclusion criteria (74.3 percent male patients), with a mean age of 38.0 +/- 17.5 years (range, 8 to 82 years). Management of traumatic optic neuropathy involved intravenous corticosteroids alone in 8.3 percent of patients (n = 9), 56.9 percent (n = 62) underwent observation, 28.4 percent (n = 31) had surgical intervention, and 6.4 percent (n = 7) underwent surgery and corticosteroid administration. Only 19.3 percent of patients returned for follow-up. Vision improved in 47.6 percent of patients, with a mean follow-up of 12.9 weeks. Patients younger than 50 years had a trend toward higher rates of visual improvement, 60 percent versus 16.7 percent (p = 0.15). CONCLUSIONS: The majority of traumatic optic neuropathy patients are unlikely to return for a follow-up examination. Optic nerve decompression has fallen out of favor in the authors' institution, and observation is the most common management strategy. Outcomes following corticosteroid administration and observation are comparable. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

BACKGROUND:Knowledge of topographic skin thickness is important to plastic surgery of the face as it may guide resection and restoration in oncologic, aesthetic, and reconstructive procedures. OBJECTIVE:The purpose of this study is to report the relative thickness of the face throughout 39 distinct subunits. METHODS:Full-thickness punch biopsy samples were obtained at 39 predetermined anatomic locations of the face from 10 human cadaveric heads. Tissue was fixed in paraffin-embedded slides and analyzed using triplicate measurement of dermis and epidermis using computerized measurements. Data were analyzed using univariate statistical analysis and expressed as mean thickness values and relative thickness (RT) values based on the thinnest portion of the face. RESULTS:The area of the face with the thickest dermis was the lower nasal sidewall (1969.2 µm, dRT: 2.59), and the thinnest was the upper medial eyelid (758.9 µm, dRT: 1.00). The area with the thickest epidermis was the upper lip (62.6 µm, eRT: 2.12), and the thinnest was the posterior auricular skin (29.6 µm, eRT: 1.00). Our results confirm that eyelid skin is the thinnest in the face. The thickest portions of the skin appeared to be in the lower nasal sidewall, but the measurements are comparable to those in the ala and posterior auricular skin, which are novel findings. CONCLUSIONS:The greatest epidermal, dermal and total skin thickness are found in the upper lip, right lower nasal sidewall, and left lower nasal sidewall respectively. The least epidermal skin thickness is in the posterior auricular skin. The least dermal skin thickness, and the least total skin thickness, are both in the upper medial eyelid.

BACKGROUND: Fractures of the mandibular condyle are common following blunt facial trauma and carry an increased risk for concomitant blunt carotid artery injuries (BCAI), a potentially life-threatening complication. Further elucidation of the relationship between specific condylar fracture patterns and BCAI may improve vascular injury screening and management. METHODS: A retrospective cohort study was performed for all craniofacial trauma patients sustaining condylar fractures that presented to a large trauma center from 2000 to 2012. Condylar fracture locations were classified according to the Strasbourg Osteosynthesis Research Group (SORG) system (SORG 1: condylar head, SORG 2: condylar neck, SORG 3: extracapsular condylar base). BCAI severity was based on the Biffl scale. Severe BCAI was defined as a Biffl score greater than I. RESULTS: We identified 605 patients with mandibular condyle fractures consisting of 21.0% (n=127) SORG 1, 26.8% (n=162) SORG 2, and 52.2% (n=316) SORG 3. Overall incidence of BCAI in this population was 5.5%(n=33), of which 75.8 % (n=25) were severe. Severe BCAIs occurred in 1.6% (n=2) of SORG 1, 2.5% (n=4) of SORG 2, and 6.0% (n=19) of SORG 3 fractures (p<0.05). SORG 3 fractures were independently associated with a 2.94-fold increased risk of a severe BCAI compared to other condyle fractures on multivariable analysis (p-value <0.05). CONCLUSIONS: The presence of extracapsular subcondylar fractures should heighten suspicion for concomitant BCAI. Our data additionally support a force transmission mechanism of injury in addition to direct vascular injuries from bony fragments.